Clinicopathological and Immunophenotypic Characteristics of Series of ZNF384 Re-arranged Acute Leukemias

Abstract

Rearrangement involving ZNF384 gene (ZNF384-r) is recently being described in acute leukemias. We present the clinic-pathological and immunophenotypic findings in a series of five cases of acute leukemia with ZNF384-r reported in our Institute between September 2020 to September 2023. Notably, while TCF3::ZNF384 fusion was the most frequently encountered abnormality, the fusion partner was not identified in two patients with ZNF384-r BCP-ALL. Immunophenotypically, patients presenting as B-cell precursor acute lymphoblastic leukemia (BCP-ALL) had a distinct profile characterized by weak or absent CD10 expression and the presence of myeloid markers such as CD13/CD33. Our findings underscore the importance of recognizing the distinct immunophenotypic features of ZNF384-r leukemias, particularly in cases presenting with atypical BCP-ALL or B/Myeloid mixed phenotype acute leukemia phenotypes. Moreover, these findings highlight the necessity for tailored diagnostic algorithms in clinical laboratories to facilitate the timely and accurate diagnosis of this clinically relevant leukemia subtype.

Keywords: BCP-ALL; Immunophenotyping; MPAL; TCF3-ZNF384 Fusion; ZNF384 Rearrangement.

Fig. 1

Multi-parametric Flow cytometry of bone marrow aspirate of case 4 reveals blasts (red population) expressing B-lineage markers CD19, CD22, and cytoCD79a; CD10 expressed in a small subset and CD20 is negative. Blasts also show positivity for myeloid and monocytic markers CD33, CD117, CD36, CD14, CD64 and a subset of blasts show cytoplasmic anti-MPO positivity and aberrant CD7 expression. Green population-Neutrophils, Blue population- Lymphocytes, Purple Population-Monocytes

Fig. 2

Fluorescent in situ hybridization in Case 5 using Cytocell SPEC ZNF384 Break apart probe showing translocation involving ZNF384 locus in chromosome 12p13.31. (Green colour-telomere end of ZNF384 locus (3’ZNF384), red colour- centromere side of ZNF384 locus (5’ZNF384). With break apart probes, normally two fusions showing two yellow-colored signals are seen, whereas in case of ZNF-r involving single allele, one red and one green signals seen indicating translocation of one allele of ZNF gene to unknown partner along with a yellow signal indicating normal ZNF384 allele are seen